Bacterial lipopolysaccharide and antimicrobial LL-37 enhance ICAM-1 expression and NF-κB p65 phosphorylation in senescent endothelial cells.
Suzuki. Kaori K; Ohkuma. Mari M; Nagaoka. Isao I
Key Findings
- Senescent endothelial cells already show higher baseline inflammation (more ICAM‑1 and NF‑κB activity) than young cells.
- Adding LL‑37 or bacterial LPS further increases ICAM‑1 expression and NF‑κB p65 phosphorylation in these senescent cells.
- Receptors that detect LPS (TLR4) and LL‑37 (P2X7) are up‑regulated in senescent endothelial cells, likely amplifying the response.
Practical Outcomes
- For biohackers, the take‑away is that boosting LL‑37 levels (e.g., via supplementation or therapies that raise its expression) might worsen vascular inflammation in older individuals, potentially accelerating plaque formation. Caution is advised when considering interventions that increase LL‑37, especially in the context of aging or cardiovascular risk. More research is needed before any protocol changes.
Summary
The study found that the antimicrobial peptide LL‑37, together with bacterial LPS, makes old (senescent) blood‑vessel cells more inflammatory by boosting a molecule called ICAM‑1 and turning on the NF‑κB pathway. This heightened inflammation could help drive atherosclerosis, especially in older people whose blood‑vessel cells are already senescent.
Abstract
Cellular senescence is associated with the induction of a proinflammatory phenotype. Notably, senescent endothelial cells are detected at the sites of atherosclerotic lesions, suggesting the involvement of senescent endothelial cells in atherogenesis. Moreover, bacterial infection has been speculated to contribute to the pathogenesis of atherosclerosis. The present study investigated the effects of Gram‑negative bacterial lipopolysaccharide (LPS) and LL‑37 (a human antimicrobial peptide of the cathelicidin family), on senescent endothelial cells, using serially passaged human endothelial cells. The results indicated that senescent endothelial cells exhibited the basal proinflammatory phenotype, as evidenced by higher intercellular adhesion molecule‑1 (ICAM‑1) expression and NF‑κB p65 phosphorylation, compared with non‑senescent cells. Additionally, exposure to LPS and LL‑37 further enhanced the expression of ICAM‑1 in senescent endothelial cells, compared with non‑senescent cells. Of note, the NF‑κB p65 pathway was more activated in senescent endothelial cells stimulated with LPS and LL‑37. Furthermore, the expression levels of the receptors for LPS and LL‑37 [toll‑like receptor 4 (TLR4) and purinergic receptor P2X 7 (P2X7), respectively] were upregulated in senescent endothelial cells. These observations indicated that LPS and LL‑37 enhanced the ICAM‑1 expression and NF‑κB p65 activation in senescent endothelial cells, potentially via the upregulated TLR4 and P2X7. Thus, senescent endothelial cells may contribute to the pathogenesis of atherosclerosis via the basal proinflammatory phenotype and the enhanced inflammatory responses against atherogenic factors, including LPS and LL‑37.
Study Information
pubmed
2019
2019-07-31T00:00:00.000Z
10.3892/ijmm.2019.4294
23
43